Roles of Hippocampal Alpha 6 GABAA Receptors in Clomipramine Alleviating Chronic Repeated Restraint Stress-Induced Depressive Behaviors in Rats

作者：Linjie Yang, Shanshan Qi, Ran Qiu, Fang Wang, 韦红巧, Zhenbo Feng · 发表于：CNS & Neurological Disorders - Drug Targets · 年份：2026 · DOI：10.2174/0118715273460368260324103547 · 研究领域：Neurotransmitter Receptor Influence on Behavior、Tryptophan and brain disorders、Neuroscience and Neuropharmacology Research

Introduction: GABAergic deficits are involved in depressive disorders; the roles of hippocampal GABAA receptors in the pathogenesis and pharmacotherapy of depression have not been fully studied. The hippocampal alpha 6 GABAA receptors (α6, Gabra6) have a critical role in the pathophysiology of major depressive disorder. The present study determined the roles of α6 subunits in the pathogenesis and antidepressant treatment of depression in a rat model of major depression induced by Chronic Repeated Restraint (CRR). Materials and Methods: Male Sprague-Dawley rats were restrained daily in an air-accessible Plexiglas cylindrical restrainer. The tricyclic antidepressant clomipramine was provided to rats daily by drinking (50 mg/kg) after restraint stress. The novelty suppressed feeding tests, open field tests, and sucrose preference tests were performed to evaluate depressive behaviors in rats. QPCR was performed to measure Gabra6 mRNA levels in rat hippocampus, and immunohistochemistry was performed to detect α6 protein localization in the hippocampus. The patch-clamp technique was used to test the electrophysiological characteristics of evoked inhibitory postsynaptic currents (eIPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) in hippocampal CA1 pyramidal neurons. Results: We observed that CRR stress decreased sucrose preference, travel distance, and center time in the open field test, and increased latency to feed in the novelty-suppressed feeding test. α6 subunit...